Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats

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Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats

Salomé, Nicolas (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology

Haage, David (author): Gothenburg University,Göteborgs universitet,Umeå universitet,Fysiologi,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology

Perrissoud, Daniel (author)

Moulin, Aline (author)

Demange, Luc (author)

Egecioglu, Emil, 1977 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology

Fehrentz, Jean-Alain (author)

Martinez, Jean (author)

Dickson, Suzanne L., 1966 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology

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Elsevier, 2009
2009
English.
In: European Journal of Pharmacology. - : Elsevier. - 0014-2999 .- 1879-0712. ; 612:1-3, s. 167-173

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; https://gup.ub.gu.se...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Here we provide the first pharmacological exploration of the impact of acute central nervous system exposure to three recently developed ghrelin receptor (GHS-R1A) ligands on food intake and on the electrical activity of the target cells for ghrelin in the hypothalamus. Central (i.c.v) injection of GHS-R1A antagonists to rats suppressed food intake induced by i.c.v ghrelin injection (1 mu g) in a dose-dependent manner with a total blockade at concentraions of 0.4 mu g and 8 mu g for JMV 3002 and JMV 2959 respectively. JMV 2810, a partial agonist, also suppressed ghrelin-induced food intake (range: 0.02-2 mu g). Moreover all three compounds reduced fasting-induced food intake in rats (i.e. the amount of food eaten during the first hour of food exposure after a 16 h fast). At the single cell level we also explored the effects of the compounds to suppress ghrelin (0.5 mu M)-induced changes in electrical activity of arcuate nucleus cells recorded extracellularly in a slice preparation. Preincubation followed by perfusion with the GHS-R1A ligands suppressed the responsiveness of arcuate cells to ghrelin. Thus, the recently developed GHS-R1A ligands (JMV 3002, 2959 and 2810) suppress ghrelin-induced and fasting-induced food intake at the level of the central nervous system. This appears to be mediated, at least in part, by a modulation of the activity of ghrelin-responsive arcuate nucleus cells. As the central ghrelin signalling system has emerged as an important pro-obesity target, it will be important to establish the efficacy of these GHS-R1A ligands to reduce fast mass in clincal studies.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Samhällsfarmaci och klinisk farmaci (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Social and Clinical Pharmacy (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)

Keyword

Arcuate nucleus
Feeding
Food intake
Growth hormone secretagogue
Hypothalamus
Neuropeptide Y

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By the author/editor: Salomé, Nicolas; Haage, David; Perrissoud, Dani ...; Moulin, Aline; Demange, Luc; Egecioglu, Emil, ...; show more...; Fehrentz, Jean-A ...; Martinez, Jean; Dickson, Suzanne ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Social and Clini ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

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By the university: Umeå University; University of Gothenburg

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